E. Bernit

Q fever 1985-1998. Clinical and epidemiologic features of 1,383 infections.

In order to describe the clinical features and the epidemiologic findings of 1,383 patients hospitalized in France for acute or chronic Q fever, we conducted a retrospective analysis based on 74,702 sera tested in our diagnostic center, National Reference Center and World Health Organization Collaborative Center for Rickettsial Diseases. The physicians in charge of all patients with evidence of acute Q fever (seroconversion and/or presence of IgM) or chronic Q fever (prolonged disease and/or IgG antibody titer to phase I of Coxiella burnetii > or = 800) were asked to complete a questionnaire, which was computerized. A total of 1,070 cases of acute Q fever was recorded. Males were more frequently diagnosed, and most cases were identified in the spring. Cases were observed more frequently in patients between the ages of 30 and 69 years. We classified patients according to the different clinical forms of acute Q fever, hepatitis (40%), pneumonia and hepatitis (20%), pneumonia (17%), isolated fever (17%), meningoencephalitis (1%), myocarditis (1%), pericarditis (1%), and meningitis (0.7%). We showed for the first time, to our knowledge, that different clinical forms of acute Q fever are associated with significantly different patient status. Hepatitis occurred in younger patients, pneumonia in older and more immunocompromised patients, and isolated fever was more common in female patients. Risk factors were not specifically associated with a clinical form except meningoencephalitis and contact with animals. The prognosis was usually good except for those with myocarditis or meningoencephalitis as 13 patients died who were significantly older than others. For chronic Q fever, antibody titers to C. burnetii phase I above 800 and IgA above 50 were predictive in 94% of cases. Among 313 patients with chronic Q fever, 259 had endocarditis, mainly patients with previous valvulopathy; 25 had an infection of vascular aneurysm or prosthesis. Patients with endocarditis or vascular infection were more frequently immunocompromised and older than those with acute Q fever. Fifteen women were infected during pregnancy; they were significantly more exposed to animals and gave birth to only 5 babies, only 2 with a normal birth weight. More rare manifestations observed were chronic hepatitis (8 cases), osteoarticular infection (7 cases), and chronic pericarditis (3 cases). Nineteen patients were observed who experienced first a documented acute infection, then, due to underlying conditions, a chronic infection. To our knowledge, we report the largest series of Q fever to date. Our results indicate that Q fever is a protean disease, grossly underestimated, with some of the clinical manifestations being only recently reported, such as Q fever during pregnancy, chronic vascular infection, osteomyelitis, pericarditis, and myocarditis. Our data confirm that chronic Q fever is mainly determined by host factors and demonstrate for the first time that host factors may also play a role in the clinical expression of acute Q fever.

Igg4-related Systemic Disease: Features and Treatment Response in a French Cohort

AbstractIgG4-related systemic disease is now recognized as a systemic disease that may affect various organs. The diagnosis is usually made in patients who present with elevated IgG4 in serum and tissue infiltration of diseased organs by numerous IgG4+ plasma cells, in the absence of validated diagnosis criteria. We report the clinical, laboratory, and histologic characteristics of 25 patients from a French nationwide cohort. We also report the treatment outcome and show that despite the efficacy of corticosteroids, a second-line treatment is frequently necessary. The clinical findings in our patients are not different from the results of previous reports from Eastern countries. Our laboratory and histologic findings, however, suggest, at least in some patients, a more broad polyclonal B cell activation than the skewed IgG4 switch previously reported. These observations strongly suggest the implication of a T-cell dependent B-cell polyclonal activation in IgG4-related systemic disease, probably at least in part under the control of T helper follicular cells.

Usefulness of 2‐[18F]‐fluoro‐2‐deoxy‐d‐glucose–Positron Emission Tomography/Computed Tomography for Staging and Evaluation of Treatment Response in IgG4‐Related Disease: A Retrospective Multicenter Study

To evaluate the usefulness of 2‐[18F]‐fluoro‐2‐deoxy‐d‐glucose–positron emission tomography/computed tomography (FDG‐PET/CT) in IgG4‐related disease (IgG4‐RD) for the staging of the disease and the followup under treatment.

Pathologies Associated with Serum IgG4 Elevation

Statement of Purpose. IgG4-related disease (IgG4-RD) is usually associated to an increase of serum IgG4 levels. However other conditions have also been associated to high serum IgG4 levels. Methods. All IgG subclasses analyses performed in our hospital over a one-year period were analyzed. When IgG4 level were over 1.35 g/L, the patients clinical observation was analyzed and both final diagnosis and reason leading to IgG subclasses analysis were recorded. Only polyclonal increases of IgG4 were considered. Summary of the Results. On 646 IgG subclass analysis performed, 59 patients had serum IgG4 over 1.35 g/L. The final diagnosis associated to serum IgG4 increase was very variable. Most patients (25%) presented with repeated infections, 13.5% with autoimmune diseases, and 10% with IgG4-RD. Other patients presented with cancer, primary immune deficiencies, idiopathic interstitial lung disease, cystic fibrosis, histiocytosis, or systemic vasculitis and 13.5% presented with various pathologies or no diagnosis. Mean IgG4 levels and IgG4/IgG ratio were higher in IgG4-RD than in other pathologies associated to elevated IgG4 levels. Conclusions. Our study confirms that elevation of serum IgG4 is not specific to IgG4-RD. Before retaining IgG4-RD diagnosis in cases of serum IgG4 above 1.35 g/L, several other pathological conditions should be excluded.

Prospective investigation of a large outbreak of meningitis due to echovirus 30 during summer 2000 in marseilles, france.

Abstract: Enteroviruses (EVs) are responsible for an array of clinical diseases affecting different systems of the organism. Many cases are asymptomatic; the most severe clinical syndromes caused by EVs are due to infection of the central nervous system and present as aseptic meningitis or encephalitis. We report here a large outbreak of enteroviral meningitis that spread in Marseilles, France, during the year 2000. The dominant strain of the outbreak was genetically identified as a human echovirus 30. The study was conducted prospectively from May to December 2000, with an investigative protocol recording epidemiologic, clinical, and laboratory data. A total of 250 patients with febrile neurologic manifestations were included between May 15 and December 30, 2000. A total of 195 cerebrospinal fluid (CSF) samples, 114 throat swabs, and 85 stool specimens were processed through viral culture and resulted in respectively 117 (60%), 61 (54%), and 58 (68%) cultures positive for EV; 69/106 (65%) CSF samples tested positive for the presence of EV RNA. None of the throat swab cultures but 5 of the stool cultures in control patients were positive. One hundred thirty-nine (55.6%) patients were considered confirmed cases because they had positive culture or reverse transcription polymerase chain reaction (RT-PCR) in CSF, and 38 (15.2%) patients were considered probable cases because they had a positive throat and/or stool culture and a negative (or not performed) procedure in CSF. The 177 confirmed and probable cases were not significantly different from the remaining 73 patients in terms of age distribution and epidemiologic, clinical, and biologic characteristics. The median age was 18.4 years (range, 15 d to 84 yr), and 92% of patients were younger than 40 years old. The male:female sex ratio was 1.8:1. We found no evidence of cases spread in nosocomial, household, or institutional settings, or limited community spread. All patients were immunocompetent except 4 adults. Meningoencephalitis represented 5.6% of cases. All but 3 of the 177 patients had a good outcome without sequelae. Two immunocompetent adults with meningoencephalitis had neurologic sequelae and an immunosuppressed adult had a fatal outcome. Upper respiratory symptoms were noted in 18.5% of patients, diarrhea in 11.5%, various types of rash in 4.5%, and myalgia in 3.8%. In CSF, white cell count was elevated in 90% of cases, with a percentage of neutrophils >50% in 55% of cases. Protein level was increased in 43% of cases. In blood, C-reactive protein was elevated in 67% of cases. Other blood parameters were unremarkable. Clinical and laboratory features did not differ from those related to other pathogens that caused meningitis and meningoencephalitis. Hence, unnecessary treatment for other infections is frequently instituted during EV infections. Virologic diagnosis is important to distinguish between EV and other treatable bacterial and viral diseases. Abbreviations: CSF = cerebrospinal fluid; ECV-30 = Echovirus 30; EV = enterovirus.

Subcutaneous immunoglobulin administration: an alternative to intravenous infusion as adjuvant treatment for dermatomyositis?

Monthly high-dose intravenous administration of human polyclonal immunoglobulins (IVIG) has been shown to be effective as an adjuvant treatment for dermatomyositis. We report a patient with dermatomyositis treated with high doses of immunoglobulins by subcutaneous infusion (SCIG). SCIG was used because of the lack of peripheral and central vein access to continue effective IVIG therapy. The treatment was administered at home, was well tolerated, and was associated to the stabilization of the disease after a 1-year follow-up. Thus, our report suggests that SCIG could be an alternative to IVIG in the treatment of dermatomyositis.

Emerging role of Raoultella ornithinolytica in human infections: a series of cases and review of the literature.

BACKGROUND Raoultella ornithinolytica is known to inhabit aquatic environments. The clinical features and outcomes of human infections caused by R. ornithinolytica have been reported for only a limited number of cases. METHODS A retrospective study of cases of infection caused by R. ornithinolytica managed at four university hospital centres during the period before and after the introduction of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed. The aim was to describe the clinical and microbiological characteristics, treatments, and outcomes. RESULTS Among 187 R. ornithinolytica isolates identified for which clinical information was available, 71 were considered colonizers and 116 were pathogenic. A total of 112 cases of R. ornithinolytica infection were identified. Urinary tract infections, gastrointestinal infections, wound and skin infections, and bacteraemia were observed in 36%, 14%, 13%, and 5% of cases, respectively. Associated infections that have been poorly reported, such as respiratory infections, i.e. pneumonia and pleural effusion, were observed in 24% of cases. Additional diseases reported here for the first time included osteomyelitis, meningitis, cerebral abscess, mediastinitis, pericarditis, conjunctivitis, and otitis. The proportion of R. ornithinolytica isolates resistant to antibiotics was found to be relatively high: 4% of isolates were resistant to ceftriaxone, 6% to quinolones, and 13% to co-trimoxazole. The mortality rate related to infection was 5%. CONCLUSIONS R. ornithinolytica is an underreported, emerging hospital-acquired infection and is particularly associated with invasive procedures. R. ornithinolytica should never be considered simply a saprophytic bacterium that occasionally contaminates bronchial lavage or other deep respiratory samples or surgical sites. Physicians should be aware of the high rates of antimicrobial resistance of R. ornithinolytica isolates so that immediate broad-spectrum antibiotic treatment can be established before accurate microbiological results are obtained.

Platelet and not erythrocyte microparticles are procoagulant in transfused thalassaemia major patients.

The level of circulating platelet‐, erythrocyte‐, leucocyte‐ and endothelial‐derived microparticles detected by high‐sensitivity flow cytometry was investigated in 37 β‐thalassaemia major patients receiving a regular transfusion regimen. The phospholipid procoagulant potential of the circulating microparticles and the microparticle‐dependent tissue factor activity were evaluated. A high level of circulating erythrocyte‐ and platelet‐microparticles was found. In contrast, the number of endothelial microparticles was within the normal range. Platelet microparticles were significantly higher in splenectomized than in non‐splenectomized patients, independent of platelet count (P < 0·001). Multivariate analysis indicated that phospholipid‐dependent procoagulant activity was influenced by both splenectomy (P = 0·001) and platelet microparticle level (P < 0·001). Erythrocyte microparticles were not related to splenectomy, appear to be devoid of proper procoagulant activity and no relationship between their production and haemolysis, dyserythropoiesis or oxidative stress markers could be established. Intra‐microparticle labelling with anti‐HbF antibodies showed that they originate only partially (median of 28%) from thalassaemic erythropoiesis. In conclusion, when β‐thalassaemia major patients are intensively transfused, the procoagulant activity associated with thalassaemic erythrocyte microparticles is probably diluted by transfusions. In contrast, platelet microparticles, being both more elevated and more procoagulant, especially after splenectomy, may contribute to the residual thrombotic risk reported in splenectomized multi‐transfused β‐thalassaemia major patients.

Agglutinines froides, circonstances de découverte chez l’adulte et signification en pratique clinique : analyse rétrospective à propos de 58 patients

PURPOSE To describe clinical, biological characteristics and associated diseases of cold agglutinins in adults. METHODS Retrospective study in a single department of internal medicine from 1997 to 2002. The inclusion criteria were a positive direct Coombs test and a positive research for cold-reactive autoantibodies. We recorded for each patient: clinical presentation at onset and during follow-up, biological parameters of haemolysis, biological characteristics of the cold agglutinin and associated diseases. RESULTS Fifty-eight patients (34 females, 24 males), with medium age of 58.8 were included in the study. Clinical presentation was highly variable between acute life-threatening haemolysis and absence of symptoms. Results of direct antiglobulin test were C3 (74%), IgG + C3 (22.4%), IgG (3.4%). Titer, thermal amplitude, strength and specificity of Coombs test were correlated, in all cases except 6, with cold agglutinin haemolytic activity. In 77.6% of cases cold agglutinin was secondary; related to: autoimmune disorders (n = 19), lymphoproliferative disorders (n = 11) and infections (n = 10). CONCLUSION Clinical presentation of cold agglutinin is highly variable and not always related to the biological characteristics of the bound antibody (titer, thermal amplitude, specificity). In our single center study, diseases associated with cold agglutinin were various with the highest frequency of auto-immune disorders. Our study underlined also the high frequency of lymphoproliferative disorders and justifies a close follow-up of these patients. Finally, we reported a high frequency of hepatitis C virus infection among the infectious aetiologies.

T Cell Polarization toward TH2/TFH2 and TH17/TFH17 in Patients with IgG4-Related Disease

IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease’s pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocytes’ subsets were analyzed by flow cytometry, with analysis of TH1/TH2/TH17, TFH cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy controls and to patients with primary Sjögren’s syndrome. Patients with IgG4-RD showed an increase of circulating T regulatory, TH2, TH17, and CD4+CXCR5+PD1+ TFH cell subsets. Accordingly, increased levels of IL-10 and IL-4 were measured in IgG-RD patients. TFH increase was characterized by the specific expansion of TFH2 (CCR6−CXCR3−), and to a lesser extent of TFH17 (CCR6+CXCR3−) cells. Interestingly, CD4+CXCR5+PD1+ TFH cells normalized under treatment. IgG4-RD is characterized by a shift of circulating T cells toward a TH2/TFH2 and TH17/TFH17 polarization. This immunological imbalance might be implicated in the disease’s pathophysiology. Treatment regimens targeting such T cells warrant further evaluation.